The olfactory receptor gene repertoire in primates and mouse: evidence for reduction of the functional fraction in primates

Abstract

Olfactory receptors (ORs) located in the cell membrane of olfactory sensory neurons of the nasal epithelium are responsible for odor detection by binding specific odorant ligands. Primates are thought to have a reduced sense of smell (microsmatic) with respect to other mammals such as dogs or rodents. We have previously demonstrated that over 70% of the human OR genes have become nonfunctional pseudogenes, leading us to hypothesize that the reduced sense of smell could correlate with the loss of functional genes. To extend these results, we sampled the OR gene repertoire of 10 primate species, from prosimian lemur to human, in addition to mouse. About 221 previously unidentified primate sequences and 33 mouse sequences were analyzed. These sequences encode ORs distributed in seven families and 56 subfamilies. Analysis showed a high fraction ( approximately 50% on average) of pseudogenes in hominoids. In contrast, only approximately 27% of OR genes are pseudogenes in Old World monkeys, and New World monkeys are almost free of pseudogenes. The prosimian branch seems to have evolved differently from the other primates and has approximately 37% pseudogene content. No pseudogenes were found in mouse. With the exception of New World monkeys, we demonstrate that primates have a high fraction of OR pseudogenes compared with mouse. We hypothesize that under relaxed selective constraints, primates would have progressively accumulated pseudogenes with the highest level seen in hominoids. The fraction of pseudogenes in the OR gene repertoire could parallel the evolution of the olfactory sensory function.

Figure 1

Schematic phylogeny tree of the primate species used in the present study (adapted from ref. 32).

Figure 2

Comparison of the deduced protein OR sequences obtained from the different primate species characterized in this study. The dendogram was established with the pileup program from the GCG Package. Percentage of ASI was determined by pairwise sequence comparisons with the gap program and is indicated along the abscissa of the tree. Sequences from the literature are indicated by asterisks. Human OR sequences derived from the use of the OR5B-OR3B primers and representing the main OR families were selected from refs. and . Dog (CfOLF1, its human counterpart HsOLF1, and CfOLF2) and chicken (COR4) sequences were selected from refs. and , respectively. OR families (greater than 40% ASI) are indicated by pink circles, and subfamilies (greater than 60% ASI) are indicated by yellow squares. The main family was arbitrarily named family 1 and subdivided into two subfamily groups, 1-I and 1-II (ovals). Group 1-II comprises subfamilies A and B. Beside the sequence names, green dots indicate sequences derived from the use of the OR5B-OR3B consensus primers; red squares indicate sequences derived from the OR3.1–7.1 consensus primers; and blue rectangles indicate potentially functional genes (uninterrupted ORFs). In the case of HSA 912–93 (blue rectangle and double asterisk), this sequence contains only one nonsense point mutation in human but is potentially coding in other primates (ref. ; see also Table 1).